Chloride → HCID 178511563, compound

HRID 22949Notes

Reaction equation

HRID 22949 reaction equation
[CH2:1]([N:3]([CH2:6][CH3:7])[CH2:4][CH3:5])[CH3:2].CS(Cl)(=O)=[O:10].[Cl-].C(OC([NH:24][C@H:25]1[CH2:30][CH2:29][C@H:28]([C:31]([N:33]2[CH2:41][C:40]3[C:35](=[CH:36]C=[C:38](CO)[CH:39]=3)[CH2:34]2)=[O:32])[CH2:27][CH2:26]1)=O)C1C=CC=CC=1>O>[O:10]1[CH2:5][CH2:4][N:3]([CH2:6][C:7]2[CH:36]=[C:35]3[C:40](=[CH:39][CH:38]=2)[CH2:41][N:33]([C:31]([C@H:28]2[CH2:27][CH2:26][C@H:25]([NH2:24])[CH2:30][CH2:29]2)=[O:32])[CH2:34]3)[CH2:1][CH2:2]1

Participants

6

Reactant 4

HCID 312ChlorideHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 178523771HCID 178523771, compound

Product 1

HCID 178511563HCID 178511563, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

0.15 ml of triethylamine and 0.07 ml of methanesulfonyl chloride were added to 10 ml of a tetrahydrofuranmethylene chloride suspension containing 0.31 g of N-benzyloxycarbonyl-trans-4-[(5-hydroxylmethyl-2-isoindolinyl)carbonyl]cyclohexylamine under ice-cooling, and the mixture was stirred under ice-cooling for 1 hour. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. After the extract was dried over sodium sulfate, the solvent was removed under reduced pressure. To the residue were added 5 ml of dimethylformamide and 0.25 ml of morpholine, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. After the extract was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure. The residue was purified by silica gel chromatography (solvent: chloroform-methanol=100:1). This compound was treated with palladium-carbon under hydrogen atmosphere to obtain trans-4-[(5-morpholinomethyl-2-isoindolinyl)carbonyl]cyclohexylamine (Reference Example 13-24 in Table 8).

Workup

  1. temperaturecooling
  2. temperaturecooling for 1 hour
  3. extractionthe mixture was extracted with ethyl acetate
  4. dry with materialAfter the extract was dried over sodium sulfate
  5. customthe solvent was removed under reduced pressure
  6. additionTo the residue were added 5 ml of dimethylformamide and 0.25 ml of morpholine
  7. stirringthe mixture was stirred at room temperature overnight
  8. additionWater was added to the reaction mixture
  9. extractionthe mixture was extracted with ethyl acetate
  10. dry with materialAfter the extract was dried over anhydrous sodium sulfate
  11. customthe solvent was removed under reduced pressure
  12. customThe residue was purified by silica gel chromatography (solvent: chloroform-methanol=100:1)
  13. additionThis compound was treated with palladium-carbon under hydrogen atmosphere

Sources & evidence

ORD record
ord-7ceede82572049f485f3af7c071223a5
Source dataset
uspto-grants-2005_02
Patent number
US06849622B2

Reaction notes

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